Maternal hypertension, antihypertensive medication use, and the risk of severe hypospadias

BACKGROUND: Hypertensive disorders occur in an estimated 5–10% of pregnancies, but few studies have examined birth defects in relation to high blood pressure and antihypertensive medication use. The objective of this study was to investigate the relationship between high blood pressure, antihypertensive medication use, and severe hypospadias. METHODS: We used data from the National Birth Defects Prevention Study, a population-based, multicenter, case-control study of birth defects to assess risks for severe hypospadias in relation to self-reported high blood pressure and prenatal exposures to antihypertensive drugs in 758 male infants with severe hypospadias and 2,058 male controls born between 1997 and 2002. Logistic regression analyses estimated ORs and 95% CIs, adjusted for potential confounders. RESULTS: We observed slight to moderate elevations in the risk of severe hypospadias for maternal untreated hypertension (adjusted OR 2.1; 95% CI: 1.6–2.9) and antihypertensive medication use during 1 month preconception through pregnancy month 4 (adjusted OR 1.4; 95% CI: 0.7–2.9). The association was strongest for subjects initiating medications after the fourth month (adjusted OR 5.0; 95% CI: 1.9–12.9). CONCLUSIONS: We observed an association between hypertension, antihypertensive medication use, and the risk of severe hypospadias, particularly when medication use began late in pregnancy. Because hypospadias occurs in early pregnancy, the data suggest that hypertension and its morphologic/physiologic precursors play an etiologic role, perhaps via compromised uteroplacental perfusion. Birth Defects Research (Part A) 82:34–40, 2008. 2007 Wiley-Liss, Inc. y